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Levy Library Blog

Article in the Spotlight: October 2021

by Angelyn Thornton on 2021-10-20T08:00:00-04:00 | Comments



Each month Levy Library showcases the achievements of Mount Sinai faculty and researchers by highlighting an article and its altmetrics. Altmetrics are alternative measures of impact that capture non-traditional data like abstract views, article downloads, and social media activity. Our altmetrics data is provided by the PlumX platform.

This month we highlight SARS-CoV-2 mRNA vaccines induce persistent human germinal centre responses. This article was written in part by Florian Krammer, PhD and Fatima Amanat




SARS-CoV-2 mRNA-based vaccines are about 95% effective in preventing COVID-191,2,3,4,5. The dynamics of antibody-secreting plasmablasts and germinal centre B cells induced by these vaccines in humans remain unclear. Here we examined antigen-specific B cell responses in peripheral blood (n = 41) and draining lymph nodes in 14 individuals who had received 2 doses of BNT162b2, an mRNA-based vaccine that encodes the full-length SARS-CoV-2 spike (S) gene1. Circulating IgG- and IgA-secreting plasmablasts that target the S protein peaked one week after the second immunization and then declined, becoming undetectable three weeks later. These plasmablast responses preceded maximal levels of serum anti-S binding and neutralizing antibodies to an early circulating SARS-CoV-2 strain as well as emerging variants, especially in individuals who had previously been infected with SARS-CoV-2 (who produced the most robust serological responses). By examining fine needle aspirates of draining axillary lymph nodes, we identified germinal centre B cells that bound S protein in all participants who were sampled after primary immunization. High frequencies of S-binding germinal centre B cells and plasmablasts were sustained in these draining lymph nodes for at least 12 weeks after the booster immunization. S-binding monoclonal antibodies derived from germinal centre B cells predominantly targeted the receptor-binding domain of the S protein, and fewer clones bound to the N-terminal domain or to epitopes shared with the S proteins of the human betacoronaviruses OC43 and HKU1. These latter cross-reactive B cell clones had higher levels of somatic hypermutation as compared to those that recognized only the SARS-CoV-2 S protein, which suggests a memory B cell origin. Our studies demonstrate that SARS-CoV-2 mRNA-based vaccination of humans induces a persistent germinal centre B cell response, which enables the generation of robust humoral immunity.


Fig. 1: Plasmablast and antibody response to SARS-CoV-2 immunization.
a, Study design. Forty-one healthy adult volunteers (ages 28–73, 8 with a history of SARS-CoV-2 infection) were enrolled and received the BNT162b2 mRNA SARS-CoV-2 vaccine. Blood was collected before immunization, and at 3, 4, 5, 7 and 15 weeks after immunization. For 14 participants (ages 28–52, none with a history of SARS-CoV-2 infection), FNAs of ipsilateral axillary lymph nodes (LNs) were collected at 3, 4, 5, 7 and 15 weeks after immunization. bc, ELISpot quantification of S-binding IgG- (b) and IgA- (c) secreting plasmablasts (PBs) in blood at baseline, and at 3, 4, 5 and 7 weeks after immunization in participants without (red) and with (black) a history of SARS-CoV-2 infection. d, Plasma IgG titres against SARS-CoV-2 S (left) and the RBD of S (right) measured by ELISA in participants without (red) and with (black) a history of SARS-CoV-2 infection at baseline, and at 3, 4, 5, 7 and 15 weeks after immunization. Dotted lines indicate limits of detection. Symbols at each time point in bd represent one sample (n = 41). Results are from one experiment performed in duplicate.


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